Mothers' Diabetes Linked to Risk of Autism

Researchers have identified an unusual risk for a child developing autism: his mother’s diabetes. Several studies found that pregnant women with diabetes – including the temporary kind – had a higher risk of delivering a child with autism than mothers who weren't diabetic.1, 2, 3, 13

This research is important because the rate of diabetes, like the rate of autism spectrum disorder (ASD), has been rising in recent decades. Gestational diabetes, a temporary condition that only occurs during pregnancy, affects as many as one in 11 expectant mothers. Cases of another form of diabetes, called Type 2, also have been rising and affecting pregnancies.4-5 Almost 3 percent of men and women ages 20 to 44 have diabetes, according to the U.S. Centers for Disease Control.

If not detected or controlled, diabetes can cause serious problems during pregnancy, including preeclampsia (dangerously high blood pressure), abnormally large babies, and difficult deliveries.6 The baby also may have problems with breathing or blood sugar after birth.5-6

Glorie Acevedo of Puerto Rico was shocked to learn she had gestational diabetes when she was 30 weeks pregnant with twins. Her diet was healthy, she said. "My doctor told me it was common. He said, 'It's not your fault. You have twins.'" She managed her diabetes through changes to her diet. It was completely controlled by the time her fraternal twins were born at 34 weeks. One twin, Diego, developed autism spectrum disorder, but he no longer shows any signs of it, said Mrs. Acevedo, who participates in Interactive Autism Network Research.

Who's at highest risk for gestational diabetes?

Many factors can increase a woman's risk for developing gestational diabetes. They include:

Having twins, which doubles the risk7

Age. Risk begins rising progressively at age 25.8

Race and ethnicity. In the United States, Asian, Hispanic, African-American, and Native American women face a higher risk that non-Hispanic whites.9-10

Being overweight or obese6

Having a family history of diabetes6

During pregnancy, hormones from the placenta can interfere with the work of the mother's insulin.5 Insulin is a hormone that transports glucose (sugar) from food into cells, where it turns into energy. Someone develops diabetes when that process malfunctions and excess sugar stays in the bloodstream. Gestational diabetes usually disappears after delivery, although those mothers are at higher risk for developing Type 2 diabetes, and their children are at risk for pre-diabetes, later in life.11

The risks for Type 2 diabetes are similar to those for gestational diabetes. Both can be managed through diet and exercise, pills and/or insulin shots. In Type 1 diabetes, people are usually diagnosed in childhood and require daily injections of insulin.

What's the autism-diabetes link?

Scientists have been trying to tease out the relationship between a mother's diabetes and her child's autism in recent years.

Researchers at Kaiser Permanente Southern California examined the prenatal records of more than 322,000 mothers; almost 3,400 of their children were later diagnosed with autism. In analyzing data, they took into account other factors that could affect the results, such as a mother's age, race, ethnicity, level of education, and history of heart, lung, kidney or liver disease, or cancer. They also looked at smoking and weight in a subset of the mothers. They made those adjustments to ensure they were only calculating the effect of diabetes on autism risk.1

They found that moms diagnosed with gestational diabetes by 26 weeks of pregnancy were 42 percent more likely to have a child with autism, compared to women without diabetes.1 To put it in perspective, the risk of having a child with autism is about 1.5 percent; gestational diabetes raises the risk to a little over 2 percent, according to that study.

Interestingly, women who were diagnosed with diabetes after 26 weeks of pregnancy did not have a higher risk of having a child with ASD. Perhaps that is because those children were exposed to high blood sugar after a period of critical brain development had passed, or because their mothers' diabetes was mild, the researchers speculated.1 In the United States, most doctors screen pregnant women for diabetes between their 24th and 28th week of pregnancy because that is when gestational diabetes usually develops.

What about other forms of diabetes?

The same lead researcher, biostatistician Anny Hui Xiang, PhD, studied mothers with Type 1 and Type 2 diabetes in a later study about autism risk in their babies. Her team looked at more than 400,000 children delivered at Kaiser Permanente Southern California hospitals from 1995 through 2012. Children born to mothers with Type 1 or Type 2 diabetes while pregnant with them had a higher risk of being diagnosed with autism than children whose moms did not have any form of diabetes. Dr. Xiang's group again found a higher autism risk with gestational diabetes diagnosed by 26 weeks of pregnancy. Gestational diabetes is more common in pregnant women than either Type 1 or Type 2 diabetes.16

What happens when a mother has obesity and diabetes?

Across the country, researchers launched two similar diabetes-autism studies, but with a few crucial differences. One group studied a group of mothers in Boston with a higher rate of obesity and diabetes than average.2 Being obese raises the risks of developing Type 2 diabetes12 and gestational diabetes.6

"The global epidemics of obesity and diabetes affect all ages, including pregnant women," said Xiaobin Wang, MD, one of the researchers. They wondered: Did having both conditions produce a combined effect that was greater than having just diabetes or obesity alone?

It did. According to this study, mothers who had diabetes and obesity before pregnancy were four times more likely to have a child with autism. Moms who had obesity and gestational diabetes were three times more likely to have a child with ASD. The Boston study was smaller than the one from Kaiser Permanente. Researchers analyzed the pregnancies of 2,734 women; 102 of their babies eventually were diagnosed with autism.2

The majority of those women were low-income, black or Hispanic. Do the results apply to mothers in other economic, racial or ethnic groups? "Maybe," said Dr. Wang, a professor at the Johns Hopkins Bloomberg School of Public Health. "The association between diabetes and ASD was seen across many studies of different populations," she said.

For example, an international research group reviewed 12 different studies from the United States, Canada, Australia, Sweden, and Egypt. They concluded that maternal diabetes is "significantly associated with a greater risk of ASD in the offspring."13

Another study, conducted in Cincinnati, Ohio, reached similar conclusions when examining both obesity and diabetes during pregnancy. This large study involved children seen by developmental pediatricians at Cincinnati Children's Hospital, as well as thousands of children without developmental conditions born in the same region.3 Expectant mothers who were obese or who had gestational diabetes were 1.5 times more likely to have a child with autism than other mothers in the study. Having both diabetes and obesity doubled the risk of autism in babies.3

What do these autism-diabetes studies prove?

Do these studies prove that diabetes, especially when combined with obesity, causes autism in some babies?

One of the mantras of science is that correlation (meaning a link or an association) does not equal causation. But discovering a correlation can be the first step in proving a cause and effect. One important factor in establishing a cause and effect is whether there's a scientific reason why something, in this case diabetes, might cause, contribute to, or trigger autism.

"Research is uncertain as to how, but theories include hyperglycemia [high levels of blood sugar] in the mother," explained Svena Julien, MD, assistant professor of gynecology and obstetrics at Johns Hopkins Medicine in Baltimore. "Glucose is toxic to many tissues, including the developing fetal brain.”

To combat damage caused by high sugar, Dr. Julien explained, the body releases other substances that cause inflammation, which itself is potentially harmful. Having excess body fat, which sometimes goes along with diabetes, also can create chronic inflammation, according to some researchers.13

Besides triggering inflammation, diabetes also could reduce the amount of oxygen a fetus gets.14 In short, diabetes influences the levels of insulin, oxygen, and inflammation in the womb, changing the environment in which the fetal brain is forming, Dr. Xiang's research group theorized.

Diabetes could affect the fetus through another avenue: oxidative stress. "Oxidative stress occurs during normal metabolism," the body’s process of using food and water, Dr. Julien said. "Certain substances undergo chemical reactions, and the by-products of those reactions release what are called free radicals. These substances can damage tissues and cells and lead to cell death,” she explained. A person’s antioxidants work to keep the free radicals in check. However, diabetes knocks that balance out of whack, raising the risk of oxidative stress.

Reducing risk before and during pregnancy

More research needs to be done to "determine if there is a true cause and effect" between a mother’s diabetes and her child’s autism, Dr. Julien said. Nonetheless, she and several researchers said, it's important to be aware of diabetes before and early in pregnancy, and, if diagnosed, to manage it properly.

Dr. Wang noted that obesity and diabetes can lead to complications in pregnancy, beyond a risk of autism. It's important to prevent obesity and diagnose diabetes early, "ideally before conception," she said.

A woman who is obese, has had gestational diabetes before, or has a strong family history of diabetes, could have her blood glucose levels tested before pregnancy and early in pregnancy, Dr. Julien said. Treatment early in pregnancy gives diabetic women and those at risk "the best chances to decrease the risk of autism," she said.

Recent Studies of Mothers' Diabetes and Autism Risk

Study

Population Studied

Factors Examined

Results

Kaiser Permanente1

322,323 children, 3,388 with ASD, in Southern California

Type 2 and gestational diabetes (GD)

42% risk increase for ASD when GD diagnosed by 26 weeks, no ASD increase for Type 2 or later onset of GD

Boston Birth Cohort2

2,734 children, 102 with ASD, from low-income minority population in Boston, Mass.